critical care studies summaries

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Protocol v2.0 06/12/2023
Rotherham Principal Investigator: Professor Anil Hormis


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research topic:

Glucocorticoids in adults with ARDS

trial groups:

Intervention: Dexamethasone plus usual care
Control: Usual care alone

inclusion criteria:

• Provision of informed consent
• Aged 16 years or older
• Admitted to intensive care unit or high dependency unit (ICU)
• Receiving respiratory support via invasive mechanical ventilation or non-invasive ventilatory support (non-invasive ventilatory support includes mask or helmet) or high flow nasal cannula (HFNC) >30L/min
  
• Within 72 hours of diagnosis of ARDS with moderate to severe hypoxaemia defined as:
  • a known acute clinical insult or new or worsening respiratory dysfunction (Note: this includes new deterioration at any time-point during the ICU stay), and
  • opacities on chest imaging not fully explained by effusions, lobar/lung collapse/atelectasis, or nodules, and
  • respiratory failure not fully explained by cardiac failure or fluid overload, and
  • assessment of hypoxaemia done with either PaO2/FiO2 ratio <26.7 kPa from arterial blood gases, or SpO2/FiO2 <235 with SaO2<97%

​For this trial, patients with unilateral opacities are eligible, as they would meet the definition of acute hypoxemic respiratory failure, and often have biological changes similar to ARDS. Furthermore, it is well recognised that there are differences in interpretation of chest radiography between observers (low inter observer agreement, validity, and reliability), what may appear to be a unilateral infiltrate on chest radiograph can seem bilateral infiltrates in a CT scan; and in mechanically ventilated patients radiological infiltrates can be masked in portable chest radiographs for numerous reasons.
We will include patients requiring other immunosuppressive drugs, provided there exists clinician equipoise for randomising such a patient.

exclusion criteria:

• ARDS due to microbiologically confirmed SARS-Co-V2 infection (COVID-19 ARDS)
• Major upper gastrointestinal bleeding during current hospital admission, defined as requiring endoscopy and transfusion for two or more units of packed red blood cells. This exclusion criterion will exclude patients with contraindications to the glucocorticoids on the grounds of safety.
• High dose glucocorticoids are required for a separate proven clinical indication at the time of randomisation as withholding treatments that have been deemed clinically effective, would be unethical.

Note: Low dose glucocorticoid treatments for clinical indications (defined as maximum daily dose of 200mg hydrocortisone or equivalent other steroids) is not an exclusion criterion.

• Known hypersensitivity to dexamethasone
• Infections that are not being effectively treated as determined by the treating medical team.

Note: Once infections are considered as effectively treated by the treating medical team, they are eligible for the trial.
Planned intensive care treatment withdrawal within next 24 hours as determined by the treating medical team

• Patients who are known to be pregnant
• Previous enrolment in the GuARDS trial

Exclusion criterion (3): In patients receiving low dose (defined as maximum daily dose of 200mg hydrocortisone or equivalent other glucocorticoids) for clinical indications, the decision to continue this low dose glucocorticoids post randomisation in the usual care arm, and in the intervention arm will be at the discretion of the treating physicians.

consent:

Consent
Formal consent is required for GuARDS trial. If you think your patient is in any way eligible please contact the research team (Cheryl 6060, Jake 7038, Rachael 4078) who will review the full inclusion/exclusion criteria and approach for consent.